Inhalant analgesic and anesthetic composition

ABSTRACT

The present invention relates to the novel compound difluoromethyl dichlorofluoromethyl ether (CHF2OCFCl2). The compound is prepared through selective chlorination of difluoromethyl monofluoromethyl ether. The compound is useful as an anesthetic and as a solvent and dispersant for fluorinated materials. The compound has the unusual property of causing a strong analgesic effect on mammals at light anesthetic concentrations.

United States Patent [1 1 Croix Apr. 22, 1975 INHALANT ANALGESIC ANDANESTHETIC COMPOSITION [75] Inventor:

[73] Assignee: Airco, Inc.. New York. N.Y.

[22] Filed: Oct. 9, 1973 [21] Appl. No.: 404.816

Related U.S. Application Data [62] Division of Ser. No. 314.222. Dec.11. 1971. Pat. No.

Louise S. Croix, Summit, NJ.

[52] U.S. Cl. 260/614 F [51] Int. Cl C07c 43/00; C07c 43/12 [58] Fieldof Search 260/614 F [56] References Cited UNITED STATES PATENTS2.066.905 l/l937 Booth 260/614 F OTHER PUBLICATIONS Larsen. FluorineChemistry Reviews 3. (1969). 38.

Primary E.\aminerl-loward T. Mars Attorney Agent. or Firm-Roger M.Rathbun; Edmund W. Bopp: H. Hume Mathews [57] ABSTRACT The presentinvention relates to the novel compound difluoromethyldichlorofluoromethyl ether 1 Claim, No Drawings INHALANT ANALGESIC ANDANESTHETIC COMPOSITION This is a Division of application Ser. No.314,222, filed Dec. 11, 1972, now [1.8. Pat. No. 3,806,602.

This invention relates to difluoromethyl dichlorofluoromethyl ether, itspreparation and its use in producing analgesia and anesthesia inanestheticsusceptible, airbreathing mammals. This ether has the unusualproperty of causing strong analgesia at light anesthetic levels on suchmammals.

The compound difluoromethyl dichlorofluoromethyl ether is represented bythe following formula:

CHF- OCFCI This ether is normally a clear, colorless liquid with nosignificant odor. The compound has the following physical properties:b.p. 41C. at 760 mm.; vapor pressure 470 mm. at 25C.; specific gravity1.49; and molecular weight 169. The compound is nonflammable, soda limestable, and an analgesic and anesthetic for inhalationanesthetic-susceptible mammals.

Difluoromethyl dichlorofluoromethyl ether is readily miscible with otherorganic liquids including fats and oils, and has useful solventproperties, for example, as a solvent for fluorinatcd olefins and otherfluorinatcd materials such as fluorowaxes. The ether can be used toprepare pastes and dispersions of such fluorinecontaining materialsuseful for coating and the like, and as degreasing agents.

The compound of the present invention can be prepared through theselective chlorination of direaction product CHF OCCI F can be readilyseparated from the reaction mixture by fractional distillation.

The following example illustrates the preparation of 5 difluoromethyldichlorofluoromethyl ether.

EXAMPLE Calculated for (HF-,OCl-Ch: C, 14.2; H, 0.6; F, 33.7 Found: C,13.9; H. 0.5; F, 33.8

In order to determine the usefulness of difluoromethyldichlorofluoromethyl ether as an inhalation anesthetic in respirablemixtures containing a lifesupporting amount of oxygen, a series of testswere carried out on mice. The compound tested was at least 99.5% pure asdetermined by vapor phase chromatography.

Groups of five mice were placed in a jar and exposed to a concentrationof 2.5 to 8% by volume of difluoromethyl dichlorofluoromethyl ether. Theresults of these tests were as follows:

maintenance. Rcspiration slowed. Brief cyanosis at start of recoveryperiod.

10+ 111. to pain.

"'Analgcsia was measured by reaction to pain caused by clipping tail.

fluoromethyl monofluoromethyl ether (CHF OCH- F),

according to the following equation:

CHF OCH F C1 CHF OCFCI The starting material, difluoromethylfluoromethyl ether (CHF OCH F), is a well known,

mono-- readily available material. The CHF OCH F is photo- The compounddifluoromethyl dichlorofluoromethyl ether exhibits light or low potencygeneral anesthetic properties in inhalation anesthetic-susceptiblemammals, and thus its use is particularly desirable where control overthe patient is desired. The compound is unusual in giving stronganalgesia lasting well into the recovery period, with only minimalgeneral anesthesia and very rapid recovery of walking. At full generalanesthesia levels it depresses respiration, although recovery is stillrapid. The compound is nonflammable and soda lime stable, and lendsitself well to effective use as an inhalant analgesic and anesthetic inrespirable mixtures containing life-supporting concentrations of oxygen.

The effective amounts of the CHF OCFCI to be employed depends upon thelevel of anesthesia to which the mammal is to be brought, the rate atwhich the anesthesia is to be induced, and the length of time over whichanesthesia is to be maintained. Minor volume percentages of the ethercompound of at least several percent, for example about 3 to preferablyabout 4 to 8%, can be used in respirable mixtures containinglife-supporting amounts of oxygen. The person controlling the anesthesiacan easily regulate the amount and gradually increase the amount untilthe desired plane of anesthesia is reached. By then monitoring thephysical reactions of the mammal, as is the usual procedure, theduration and plane of anesthesia can be readily controlled. Lesseramounts of the ether compound can be employed along with oxygen whereonly an analgesic effect is desired.

It should be understood that the foregoing disclosure CHF OCFCI

1. THE COMPOUND DIFLUOROMETHL DICHLOROFLUOROMETHYL ETHER REPRESENTED BYTHE FORMULA: